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1、SPARC、E-cadher i n及SnaI在胃癌中的表达及其与临床病 理特征和预后的关系捅姜目的检测富含半胱氨酸的酸性分泌蛋白(SPARC)、E钙粘素(Ecadhefin)及锌指 转录因子Snail在非肿瘤胃粘膜组织和胃癌组织中的差异表达，探讨SPARC表达 与Snail及Ecadhefin之间的关系，并进一步研究三者表达与胃癌浸润转移和预后 的关系。方法利用组织芯片技术将123例胃癌组织和4l例非肿瘤粘膜组织石蜡标本制作 成组织：签片应用免疫组化PV6000法检测非肿瘤胃粘膜组织和胃癌组织中 SPARC、Snail及Ecadhefin的表达情况。使用SPSSl60软件，对免疫组织 化学结
2、果进行统计学分析，分析SPARC、Ecadherin及Snail的表达与患者各临 床病理参数及生存期之间的关系，P005为差异有统计学意义。结果123例胃癌组织中，SPARC在癌组织周围的间质细胞的高表达与癌细胞、非 肿瘤粘膜组织间质细胞相比，SPARC高表达差异有显著性(P均005)。 Ecadherin及Snail高表达在胃癌组织与非肿瘤粘膜组织两组之间有显著性差异 (P均O05)。SPARC在胃癌间质细胞中的高表达与浸润深度、淋巴结转移 及TNM分期有关(P均O05)；Ecadherin的低表达和Snail的高表达与浸润深 度、淋巴结转移及TNM分期有关(P均005)。SPARC、Eca
3、dherin及Snail 高表达的患者与低表达的患者生存时间有显著性差异(P均O05)；CoxL匕例模 型分析EcMhefin、浸润深度、淋巴结转移和TNM分期是影响胃癌患者预后的 独立因素(P005)。胃癌中SPARC表达与Snail表达呈正相关(PO05)，而 SPARC表达与Ecadhefin表达及Ecadhefin表达与Snail表达均呈负相关(P005)。结论SPARC、snail高表达及Ecadhefin低表达可能是胃癌发生以及胃癌发生浸 润转移的重要生物学标志，联合检测SPARC、Snail及E-cadhefin对预测胃癌浸 润转移有重要意义；胃癌组织SPARC、Snail及Ec
4、adhefin的表达与胃癌患者 生存密切相关，SPARC、Ecadhefin及Snail可以作为预测胃癌不良预后的生物 学标志物。硕士研究生董明霞病理学指导教师于建宪教授 关键词：胃癌；富含半胱氨酸的酸性分泌蛋白；免疫组织化学；预后Y 川20 椰43叭5 叭4 吣5SPARC，E-cadherin and Snail expression in gastric carcinoma and relationship with characteristic of clinicpathology and prognosisAbstractObjective：Tlle expression of se
5、cretend protein acidic and rich in eysteine(SPARC)， Ecadherin and the zinc finger transcription factor Snail were detected in nonneoplastic mucosa tissue and gastric carcinoma tissue and discussed the relationship among themFurther research was used to find the relationship between their expression
6、and the invasion，metastasis and prognosis of gastric carcinomaMethods：To make 1 23 cases of gastric carcinoma tissue and 4 l cases of nonneoplastic mucosa tissue paraffin specimens in tissue microarray by tissue microarray technology PV6000 immunohistochemical staining was used to determine protein
7、expression of SPARCEcadherin and Snail in nonneoplastic mucosa tissue and gastric carcinoma tissueIt was using SPSS l 60 software to analyze those immunohistochemical results of SPARC。E-cadherin and Snail and the relationship between their expression and clinicopathological parameters of patients an
8、d survivalPO05 for the difference wassignificanceResuits：In the 1 23 cases of gastric carcinoma tissue，compared with the results of stromal cells in nonneoplastic mucosa and tumor cells，there were significant difference of high expression rates of SPARC in stromal cells around tumor cells rP005)The
9、high expression of E-cadherin and Snail were significant difference between gastric carcinoma tissue and nonneoplastic mucosa tissue(P all005)(g)The high，expression of SPARC in gastric carcinoma stromal cells was closely correlated with depth of invasion，lymph nodemetastasis and TNM staging(P all005
10、)The low expression of Ecadherin and the highexpression of Snail in gastric carcinoma tissue were closely correlated with depth of invasion，lymph node metastasis and TNM staging(P allO05)The median survival time for patients with high expression of SPARC，Ecadherin and Snail protein expression was st
11、atistically significant(p005)compared to patients with low expressionof SPARC，Ecadhefin and SnailEcadherin。depth of invasion。lymph node metastasisand pathological stages were independent prognostic factors by Cox model analysisThe expression of SPARC and the expression of Snail in gastric carcinoma
12、tissue was positively correlated(P005)；the expression of Ecadherin was negatively correlated with the expression of SPARC and Snail(P005)ConclusionThe high expression of SPARC and Snail and the lOW expression ofE-cadherin might be important biological markers for invasion and matastasis of gastric c
13、arcinoma，nle combined detection of SPARC and Snail and E-cadherin has positive effects on predicting the invasion and metastasis in gastric carcinomaThe expression of SPARC and Snail and Ecadherin in gastric carcinoma tissue was correlated with patientS survival timeTherefore，SPARC，Snail and Ecadher
14、in can be used as indicators for gastric carcinoma prognosisPostgraduate：Dong Mingxia(pathology)Derected by：profYu Jian-XianKey words：Gastric cancer；SPARC；lmmunohistochemistry(IHC)；prognosis0I青SPARC、Ecadherin及Snail在胃癌中的表达、转移及预后的关系，J、引言胃癌是世界上常见的恶性肿瘤之一，其死亡率居各种恶性肿瘤之首。我国是胃 癌的高发区，胃癌年患病率和死亡率均高于世界平均水平。早期胃癌
15、的患者治疗后 生存率明显高于进展期胃癌。胃癌的侵袭转移是患者术后复发和死亡的一个重要原 因ll之J，因此对胃癌侵袭转移的机制进行深入的研究，显得尤为重要。胃癌的侵袭转 移是一个极其复杂的生物学过程，涉及肿瘤细胞之间粘附机制的丧失，肿瘤细胞 间质细胞之间以及与细胞外基质之间的共同作用，并受多种细胞因子的影响和调控， 其中细胞粘附机制参与并起主要作用。探讨胃癌浸润和转移的生物学机制，寻找与 胃癌浸润转移相关的生物学标志物，从而提高胃癌的早期诊断率及提高胃癌患者的 预后，是当前胃癌研究的热点领域。富含半胱氨酸的酸性分泌蛋白(secretend protein acidic and rich in eysteine， SPARC)又可被称为骨连蛋白(osteonectin)、基底膜40蛋白(BM40)或43K蛋白， 是一个32kD的钙离子糖结合蛋白。它可以通过与细胞外基质相互作用及调节细胞因 子的分泌来调节细胞的生长。不同的实验室已经纯化或克隆了SPARC蛋白。SPARC 的生
